Neuroprotection is the mechanism and strategy used to protect against neuronal injury or degeneration in the CNS following acute disorders (e.g., stroke or nervous system injury/trauma) or as a result of chronic neurodegenerative diseases (e.g., Parkinson's, Alzheimer's, multiple sclerosis). The goal of neuroprotection is to limit neuronal dysfunction/death after CNS injury and attempt to maintain the highest possible integrity of cellular interactions in the brain resulting in an undisturbed neural function.
There are a wide range of neuroprotective products available or under investigation and some products can potentially be used in more than one disorder, as many of the underlying mechanisms of damage to neural tissues (in both acute disorders and in chronic neurodegenerative diseases) are similar. Products with neuroprotective effects are grouped into the following categories: free radical trappers/scavengers, anti-excitotoxic agents, apoptosis (programmed cell death) inhibitors, anti-inflammatory agents, neurotrophic factors, metal ion chelators, ion channel modulators and gene therapy.
Stroke is the rapidly developing loss of brain functions due to a disturbance in the blood vessels supplying blood to the brain, which can be due to ischemia (lack of blood supply) caused by thrombosis or embolism, or due to a hemorrhage. Stroke is the second most common cause of death and major contributor to serious physical, emotional, and cognitive deficits worldwide. (Donnan, G. A., et al., Lancet, 371(9624):1612-23 (May 2008)). The National Stroke Association states that stroke is the number one cause of adult disability in America (66% of survivors having some type of disability)—there are an estimated 15 million strokes occurring worldwide each year. Stroke is a medical emergency and can cause permanent neurological damage, complications and death if not promptly diagnosed and treated.
Ischemic stroke is the most common type, accounting for about 87% of all strokes. Rapid deprivation of oxygen and glucose to brain induces over-activation of glutamate receptors, accumulation of intracellular Ca2+, abnormal recruitment of inflammatory cells, excessive production of free radicals, leading to the spread of ischemic neuronal death. (Mehta, S. L., et al., Brain Res. Rev. 54(1):34-66 (2007); Durukan, A. and Tatlisumak T., Pharmacol. Biochem. Behav. 87(1):179-97 (2007)). Several neuroprotective agents designed to block these pathological events have been evaluated in preclinical stroke models. (Green, A. R., Br. J. Pharmacol., 153 Suppl. 1:S325-38 (2008)). However, translation of neuroprotective benefits from the laboratory bench to the emergency room has not been successful and thrombolytic therapy remains the only FDA approved acute therapy for ischemic stroke, which benefits only about 2-5% of all hospitalized stroke patients. Therefore, the need to identify safe and efficient neuroprotective agents that will benefit a larger number of acute stroke patients remains vitally important.